Lectins are molecules with specific binding sites for oligosaccharides and appear to be ubiquitous in nature. Because of the high degree of specificity, lectins show for oligosaccharide structure; and because of the large number of oligosaccharide structures which exist on cell surfaces, lectins have been proposed as candidates for cellular recognition structures. This project involves the study of lectin-saccharide recognition in the human natural cytotoxicity system. Human natural killer (NK) cells spontaneously lyse tumor cells in vitro and have been found to be deficient in some cancer patients, leading to the hypothesis that they participate in immune surveillance against tumors. NK lysis of the sensitive tumor target can be blocked with monosaccharides and glycoproteins; and K562 cells grown in tunicamycin, an antibiotic which blocks glycosylation of proteins, are insensitive to NK lysis. This project involves the isolation of glycopeptides and glycolipids from K562 membranes by lectin affinity chromatography and identification of molecules which protect K562 cells from NK lysis. The isolated glycoconjugates will be characterized in terms of oligosaccharide structure and antibodies will be made against them which then will be used to study the distribution of the blocking oligosaccharides on NK-sensitive cells. Target-specific oligosaccharides will also be used to identify and purify the specific target receptor on human NK cells. By determining the recognition structures involved in NK lysis, we should gain knowledge of the mechanism of cytotoxicity and also the possible in vivo function of NK cells, either as killers of tumor cells or as regulator cells of the immune system.